The goal of this research is to define in objective terms the steps leading to macrophage activation for tumor cell killing and regulation of this process. Gamma-interferon produced either by a T-cell hybridoma or by recombinant DNA technology has been shown to be the lymphokine that primes macrophages for tumor cell killing and that acts to maintain killing when physiological levels of PGE2 are present. The latter mediator otherwise acts to shut off the expression of killing by activated macrophages. The second triggering signal that causes primed macrophages to express cytolytic activity is currently being sought. Monoclonal antibodies are being used both to characterize the extent of heterogeneity in macrophage populations and to characterize stages of macrophage activation objectively.